Wang Lin, Lin Guiting, Lee Yung-Chin, Reed-Maldonado Amanda B, Sanford Melissa T, Wang Guifang, Li Huixi, Banie Lia, Xin Zhengcheng, Lue Tom F
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
Department of Urology, Peking University First Hospital, Peking University, Beijing, China.
BJU Int. 2017 Feb;119(2):317-324. doi: 10.1111/bju.13661. Epub 2016 Oct 5.
To study and compare the function and structure of the urethral sphincter in female Zucker lean (ZL) and Zucker fatty (ZF) rats and to assess the viability of ZF fats as a model for female obesity-associated stress urinary incontinence (SUI).
Two study arms were created: a ZL arm including 16-week-old female ZL rats (ZUC-Lepr 186; n = 12) and a ZF arm including 16-week-old female ZF rats (ZUC-Lepr 185; n = 12). I.p. insulin tolerance testing was carried out before functional study. Metabolic cages, conscious cystometry and leak point pressure (LPP) assessments were conducted. Urethral tissues were harvested for immunofluorescence staining to check intramyocellular lipid (IMCL) and sphincter muscle (smooth muscle and striated muscle) composition.
The ZF rats had insulin resistance, a greater voiding frequency and lower LPP compared with ZL rats (P < 0.05), with more IMCL deposition localized in the urethral striated muscle fibres of the ZF rats (P < 0.05). The thickness of the striated muscle layer and the ratio of striated muscle to smooth muscle were lower in ZF than in ZL rats.
Obesity impairs urethral sphincter function via IMCL deposition and leads to atrophy and distortion of urethral striated muscle. The ZF rats could be a consistent and reliable animal model in which to study obesity-associated SUI.
研究并比较雌性 Zucker 瘦素（ZL）大鼠和 Zucker 肥胖（ZF）大鼠尿道括约肌的功能和结构，并评估 ZF 大鼠作为女性肥胖相关性压力性尿失禁（SUI）模型的可行性。
设立两个研究组：ZL 组包括 16 周龄雌性 ZL 大鼠（ZUC-Lepr 186；n = 12），ZF 组包括 16 周龄雌性 ZF 大鼠（ZUC-Lepr 185；n = 12）。在功能研究前进行腹腔注射胰岛素耐量试验。进行代谢笼实验、清醒膀胱测压和漏点压力（LPP）评估。采集尿道组织进行免疫荧光染色，以检查细胞内脂质（IMCL）和括约肌肌肉（平滑肌和横纹肌）组成。
与 ZL 大鼠相比，ZF 大鼠具有胰岛素抵抗、排尿频率更高且 LPP 更低（P < 0.05），ZF 大鼠尿道横纹肌纤维中 IMCL 沉积更多（P < 0.05）。ZF 大鼠的横纹肌层厚度以及横纹肌与平滑肌的比例均低于 ZL 大鼠。
肥胖通过 IMCL 沉积损害尿道括约肌功能，并导致尿道横纹肌萎缩和变形。ZF 大鼠可能是研究肥胖相关性 SUI 的一种一致且可靠的动物模型。
